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Trial registered on ANZCTR


Registration number
ACTRN12618000260224
Ethics application status
Approved
Date submitted
13/02/2018
Date registered
19/02/2018
Date last updated
6/12/2018
Date data sharing statement initially provided
6/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Anti-chlamydophila antibiotic combination therapy in the treatment of patients with Coronary Heart Disease
Scientific title
Prospective Study to evaluate the safety and measure efficacy of anti-Chlamydophila antibiotic combination (ACAC) therapy in the treatment of patients with Coronary Heart Disease (CHD)
Secondary ID [1] 294044 0
NC10/C01
Universal Trial Number (UTN)
U1111-1209-3489
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Heart Disease 306588 0
Chlamydophila pneumoniae infection 306595 0
Condition category
Condition code
Cardiovascular 305682 305682 0 0
Coronary heart disease
Infection 305688 305688 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Anti-Chlamydaphila antibiotic combination: Doxycycline, Azithromycin & Rifabutin
Dose: 50mg Doxycycline, 250mg Azithromycin & 150mg Rifabutin (3 separate capsules) daily (days 1 to 7), 50mg Doxycycline, 250mg Azithromycin & 150mg Rifabutin (3 separate capsules) twice daily (days 8 to 90).
Duration: 90 days
Mode: oral capsules
Intervention code [1] 300317 0
Treatment: Drugs
Comparator / control treatment
Arm 2 - Identical Placebo capsule dosing
Dose: 1 capsule of each bottle (3 separate capsules) daily (days 1 to 7), 1 capsule of each bottle (3 separate capsules) twice daily (days 8 to 90).
Duration: 90 days
Mode: oral capsules
Control group
Placebo

Outcomes
Primary outcome [1] 304776 0
To evaluate the effect of antibiotic combination therapy on objective measures of improvement in coronary flow as determined by fractional flow reserve (FFR) in subjects undergoing percutaneous coronary intervention (PCI) with non-critical lesions in non-culprit arteries.
Timepoint [1] 304776 0
Day 90 post initiation of treatment (Visit 3)
Secondary outcome [1] 343140 0
To evaluate angiographic stenoses changes (QCA) via diagnostic angiography during the ACAC trial.
Timepoint [1] 343140 0
Day 90 post initiation of treatment (Visit 3)
Secondary outcome [2] 343142 0
To record major adverse clinical events (MACE), including death, recurrent myocardial infarction, stroke and major bleeding via investigator adverse event reporting
Timepoint [2] 343142 0
Day 90 (Visit 3) & Day 180 post initiation of treatment

Eligibility
Key inclusion criteria
1. Males and females (without childbearing potential as evidenced by hysterectomy, tubal ligation or at least one year post-menopause) aged 18 to 80 years, inclusive.
2. Ability to provide written informed consent to participate in the study.
3. Subjects with documented recent acute coronary syndrome (ACS) or evidence of myocardial ischemia.
4. Subjects who have a culprit lesion suitable for PCI, and a non-critical lesion in another vessel suitable for staged PCI with an FFR of <0.80, for subjects undergoing diagnostic angiography and FFR without ad hoc PCI.
5. No serious co-morbidities, which might interfere with the subject’s ability to enter the study.
6. Able to communicate effectively with the study team and to comply with the protocol.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Females that are of child bearing potential
2. Subjects without a non-culprit lesion considered appropriate to plan a staged PCI.
3. Clinically significant haematologic, hepatic, metabolic, renal, rheumatologic, anaphylactic reactions, neurological or psychiatric disease
4. Clinical evidence of any other disease, which might interfere with the subject’s ability to enter the trial.
5. Concomitant administration of medications that may interfere with treatment as assessed by the Investigator, including allergy to any component of the therapy.
6. Concomitant administration of any medication prohibited for use during this study (e.g. colchicine)
7. Male subjects consuming greater than 60g alcohol per day, or female subjects consuming greater than 40g alcohol per day.
8. Evidence of any recent history of, or current recreational drug abuse
9. Serious adverse reaction or hypersensitivity to therapeutic drugs.
10. Unable and to comply with the study requirements.
11. Subjects who have been involved in an experimental drug protocol within the past four weeks.

If a subject becomes pregnant during the course of the study, they will be immediately withdrawn and treated in the way least likely to harm both subject and foetus.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Analysis of efficacy will be performed according to intention-to-treat method and include all subjects who received the combination antibiotic therapy. However as the primary efficacy analysis is of subjects with paired FFR assessments, only such subjects will be included in the primary analysis. All other subjects will be included in secondary analyses. Numerical data will be presented as mean +/- SD for normally distributed variables and as median with interquartile range for non-normally distributed data. Non-normally distributed data will be log-transformed (e.g. CRP levels) before being used for comparisons. Significant changes in subjects’ arterial flow, clinical symptoms and biochemical variables over time compared with that baseline will be assessed using an analysis of covariance. Differences between treatment and control groups in the occurrence of FFR great than, or equal to 80 will be assessed using Fisher’s exact test. All tests will be 2-tailed with a 5% significance level.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
12/03/2018
Actual
12/04/2018
Date of last participant enrolment
Anticipated
30/06/2020
Actual
Date of last data collection
Anticipated
31/12/2020
Actual
Sample size
Target
60
Accrual to date
6
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 10008 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 10009 0
Centre for Digestive Diseases - Five Dock
Recruitment postcode(s) [1] 19334 0
2170 - Liverpool
Recruitment postcode(s) [2] 19335 0
2046 - Five Dock

Funding & Sponsors
Funding source category [1] 298669 0
Commercial sector/Industry
Name [1] 298669 0
Cadrock Pty Ltd
Country [1] 298669 0
Australia
Primary sponsor type
Hospital
Name
Centre for Digestive Diseases
Address
Level 1, 229 Great North Rd
Five Dock, NSW, 2046
Country
Australia
Secondary sponsor category [1] 297838 0
Hospital
Name [1] 297838 0
Liverpool Hospital
Address [1] 297838 0
Elizabeth St,
Liverpool NSW 2170
Country [1] 297838 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299623 0
South Western Sydney Local Health District Research & Ethics Office
Ethics committee address [1] 299623 0
Locked Bag 7103,
LIVERPOOL BC, NSW, 1871
Ethics committee country [1] 299623 0
Australia
Date submitted for ethics approval [1] 299623 0
23/01/2015
Approval date [1] 299623 0
08/06/2016
Ethics approval number [1] 299623 0
HE16/025

Summary
Brief summary
The purpose of the study is to see whether the antibiotic combination of 100mg doxycycline, 500mg azithromycin and 300mg rifabutin is a safe and effective treatment for coronary artery disease which has not responded to "standard" treatment.

Coronary artery disease is the process of plaque build up within the walls of the arteries responsible for the supplying the heart with oxygen and nutrients. Plaque is usually made up of fatty deposits, minerals and various amounts of tissue and white cells which eventually narrows the artery, reducing blood flow to the heart. The resulting damage and build up of fat results in inflammation of the arterial wall and eventually the arteries narrow. The researchers involved in this study consider that a pathogen called Chlamydophila pneumonia, which can live inside cells, may cause this inflammation of the arterial wall.

The purpose of this study is to see if treatment with this antibiotic combination in patients with CHD is safe and effective in reducing disease severity measured at coronary angiography and improving quality-of-life.

Approximately 60 patients will be involved in this trial. The treatment period is 90 days, with a further 90 day follow-up period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81070 0
Prof John French
Address 81070 0
Liverpool Hospital,
Elizabeth St, Liverpool NSW 2170, Sydney, Australia.
Country 81070 0
Australia
Phone 81070 0
+61 2 8738 3495
Fax 81070 0
Email 81070 0
[email protected]
Contact person for public queries
Name 81071 0
Annabel Clancy
Address 81071 0
Centre for Digestive Diseases
Level 1, 229 Great North Rd,
Five Dock NSW, 2046
Country 81071 0
Australia
Phone 81071 0
+61 2 9370 0032
Fax 81071 0
Email 81071 0
[email protected]
Contact person for scientific queries
Name 81072 0
Thomas Borody
Address 81072 0
Centre for Digestive Diseases
Level 1, 229 Great North Rd,
Five Dock NSW, 2046
Country 81072 0
Australia
Phone 81072 0
+61 2 9370 0011
Fax 81072 0
Email 81072 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.